Interleukin-12p70-dependent interferon- gamma production is crucial for resistance in African trypanosomiasis.

TitleInterleukin-12p70-dependent interferon- gamma production is crucial for resistance in African trypanosomiasis.
Publication TypeJournal Article
Year of Publication2007
AuthorsBarkhuizen, M., S. Magez, R. A. Atkinson, and F. Brombacher
JournalJ Infect Dis
Volume196
Issue8
Pagination1253-60
Date Published2007 Oct 15
ISSN0022-1899
KeywordsAnimals, Disease Models, Animal, Immunity, Innate, Interferon-gamma, Interleukin-12, Mice, Mice, Knockout, Parasitemia, Receptors, Interferon, Survival Analysis, Trypanosoma brucei brucei, Trypanosomiasis, African
Abstract

African trypanosomiasis encompasses diseases caused by pathogenic trypanosomes, infecting both humans and animals. In the present article, we dissected the possible role of members of the interleukin (IL)-12 family during infection with Trypanosoma brucei brucei and Trypanosoma evansi in mice. IL-12p35(-/-), IL-12p40(-/-), and IL-12p35(-/-)/p40(-/-) mice were susceptible to both pathogens, as was demonstrated by the increased mortality among these mice, compared with wild-type C57BL/6 mice. The different IL-12p70(-/-) mouse strains showed similar mortality kinetics, suggesting that IL-12p70--but not the IL-12p80 homodimer or IL-23--plays a crucial role in survival. Although there were similar plasma levels of immunoglobulin (Ig) M and IgG2a in IL-12-deficient mice and wild-type mice, interferon (IFN)- gamma production, especially during early infection, was severely impaired in all IL-12p70(-/-) mouse strains, demonstrating an IL-12p70-dependent mechanism for IFN- gamma production. Because IFN- gamma receptor-deficient mice (IFN- gamma R(-/-)) were also highly susceptible to both Trypanosoma species, IL-12p70-dependent IFN- gamma production seems to be the important mechanism involved in resistance against both pathogens.

DOI10.1086/521681
Alternate JournalJ. Infect. Dis.
PubMed ID17955445